• Progranulin (encoded by the Grn gene) is a conserved, glycosylated secreted protein, which plays a key role in the development, survival,  function and maintenance of neurons and microglia in brain. The loss-of-function mutations in Grn could lead to neuronal diseases in a gene dosage-dependent manner.
• The genome sequences between exons 2-13 in mouse Grn gene were depleted in B-Grn KO mice. As a result, mouse GRN protein will not be expressed anymore.
• Mouse Grn mRNA was only detectable in cortex, hippocampus and kidney from wild-type C57BL/6N mice, but not in B-Grn KO mice.
• This model is useful in studying the role of GRN, or the therapeutic efficacy in frontotemporal lobar degeneration.

Gene targeting strategy for B-Grn KO mice.The genome sequences between exons 2-13 in mouse Grn gene were depleted in B-Grn KO mice. As a result, mouse GRN protein will not be expressed anymore.

Strain specific analysis of Grn mRNA expression in wild-type C57BL/6N mice and B-Grn KO mice by RT-PCR. Cortex, hippocampus and kidney RNA were isolated from wild-type C57BL/6N mice (+/+) and homozygous B-Grn KO mice (-/-), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse Grn primers. Mouse Grn mRNA was only detectable in wild-type mice but not in B-Grn KO mice.